Stroke remains one of the most important neurological affection. It represents the second leading cause of preventable death worldwide and a major cause of productivity impairment. The two main subtypes of stroke are ischemic stroke (IS) and intracerebral hemorrhage (ICH), also called hemorrhagic stroke. Over 80-85% of all strokes are IS caused by a brain artery occlusion, whereas the remaining 15-20% are ICH that appear due to an arterial rupture. Patients who suffer ICH presents a poorer outcome with a mortality after 30 days from symptoms onset of 37-38%, in contrast with IS patients who have a 30-days mortality of only 8-12%.
An accurate differentiation of both subtypes is critical during acute phase to prescribe the most suitable treatment protocol, which is specific and widely different between IS and ICH. The primary therapy recommended for acute IS is thrombolysis with recombinant tissue plasminogen activator (r-tPA), a serine protease that lysates the clot that occludes the brain artery. Thrombolysis has a narrow therapeutic time window of only 4.5 h from symptoms onset, thus a rapid identification of IS might allow an early recanalization leading to a recovery of the tissue from the penumbra and therefore improving the clinical outcome. On the contrary, patients with acute ICH can be managed by reducing blood pressure in order to delay hematoma growth or to avoid edema appearance and rebleedings. Some ICH patients present underlying hemostatic abnormalities that can be due to oral anticoagulant (OACs) intake, to an acquired or congenital coagulation factor deficiency or to an abnormal platelet number or functionality. In all these cases homeostasis needs to be re-established by correcting the dose of OACs or replacing the absent coagulation factor or platelets.
Nowadays stroke subtype diagnosis is mainly based on brain imaging data by computerized tomography (CT) or magnetic resonance imaging (MRI). Unfortunately, in spite of being highly sensitive, MRI and CT scans are rarely available, cannot be used repeatedly in primary hospital due to the lack of resources and may be subject to error or uncertainty if the medical personnel conducting and/or interpreting the scan are inexperienced or inadequately trained.
Several documents describe the use of biomarkers in order to carry out a rapid differentiation of stroke subtypes, such as WO2012036892 which discloses the determination of proteins such as apolipoprotein A-I preprotein, apolipoprotein A-II preprotein, apolipoprotein A-IV preprotein, apolipoprotein B precursor, apolipoprotein C-I precursor, apolipoprotein C-II precursor, apolipoprotein C-III precursor, apolipoprotein D precursor, apolipoprotein E precursor and apolipoprotein H precursor.
Kavalci C. et al (Bratisl. Lek.Listy 3011; 112) discloses using the combination of plasma biomarkers such as BNP, D-dimer, MMP9 and S100b for differential diagnosis of ischemic or hemorrhagic stroke.
Dr. K. E. Jiehas described a summary of differential diagnostic tests for stroke subtypes, highlighting the weaknesses of the studies (www.bestbets.org/bets/bet.php?id=2251).
Thus, there is a need in the art of alternative rapid biomarker-based test to overcome the limitations of the methods disclosed in the art and that they can speed-up the process of stroke subtype diagnosis and shortening the acute treatment initiation.